Survival After Implantable Cardioverter-Defibrillator Implantation in the Elderly
Prospective randomized studies have demonstrated a survival benefit among patients with defined baseline characteristics undergoing defibrillator implantation for a primary1-5 or secondary6-8 indication. However, only a small number of patients enrolled in these landmark trials were elderly. Accordingly, concerns have been raised about the overall clinical benefit that may manifest in the elderly patient population. In this study mortality rates and appropriate shock rates were assessed in patient groups defined by the age decile at the time of defibrillator implantation.9
In this study 5399 patients enrolled in the Ontario ICD database between February, 2007 and September, 2010 were assigned to five age categories (1: 18-49, 2: 50-59, 3: 60-69, 4: 70-79, 5: ≥ 80 years). The primary endpoints were mortality and appropriate shocks. Secondary endpoints included (1) appropriate shocks or ATP, (2) inappropriate shocks, (3) device-related complications within 45 days of implantation and (4) hospitalization. The 'Canadian Institute for Health Information Discharge Abstract Database' was used to identify patient hospitalizations and the 'Registered Persons Database' was used to determine death.
Patients between the ages of 70-79 accounted for 31.6% and patients > 80 years accounted for 8.0% of enrollees in this registry. Elderly patients had higher rates of AF, hypertension, renal disease, stroke and a wider QRS. The LVEF and LA size were not different among the age groups (p<0.001 for all).
Differences were noted across age groups for the two primary endpoints. First, the appropriate shock rates did not vary among primary (p=0.139) or secondary (p=0.993) prevention patients across any of the age groups. Second, total mortality rates after ICD implantation increased with advancing age in both the primary prevention patients (age category one to five rates of 2.1, 3.3, 5.4, 6.9, 10.2 per 100 person-years [p<0.001]) and the secondary prevention patients (age category one to five rates of 2.2, 3.8, 6.1, 8.7, 15.5 per 100 person-years [p<0.001]). The mortality effect was more pronounced in the secondary than the primary prevention group. Cardiovascular and non-cardiovascular hospitalizations resulting in death were statistically higher in elderly patients. The mortality effect persisted after performance of a co-variate competing risk analysis in both the primary and secondary prevention groups.
When the secondary endpoints were assessed, there was no difference in total appropriate therapy (combination of shocks and ATP) or complications in either the primary or secondary groups across the different age groups. The inappropriate shock rate was not different in secondary prevention patients across the different age groups, p=0.488. However, younger primary prevention patients had higher inappropriate shock rates, p=0.003. Cardiac hospitalizations increased with advancing age for both primary (p=0.035) and secondary (p=0.013) indication patients.
Based upon similar rates of appropriate ICD shocks across all age groups, but higher overall mortality rates with advancing age, the authors conclude that a decision to proceed with an ICD implantation should not be based upon age alone but instead be based upon consideration of all of the clinical features, which might impact mortality.
As noted, implantable defibrillator therapy has been shown to improve mortality among patients with LV systolic dysfunction, when employed for either a primary1-5 or secondary6-8 indication. However, despite the overall mortality reduction observed in these trials, concerns persist about the potential survival benefit in select patient populations. Several studies have identified clinical features, which appear to correlate with decreased survival.10 Higher overall mortality rates in elderly patients11 have raised the possibility that increased age, in conjunction with other associated co-morbidities, might lead to higher non-arrhythmic mortality rates, higher complication rates and therefore a diminished benefit from ICD therapy.12 Unfortunately these publications, comprised mostly of post-hoc analyses, are all very limited.
Review of the published literature does not provide enough information to addresses effectively the relationship between age and mortality among ICD patients. The mean age in the major primary and secondary trials was relatively low (MADIT: 62+9, MUSTT: 60+9, MADIT II: 64+10, SCD-HeFT: 60+9, AVID: 65+11, CIDS: 63+9, CASH: 64+10).1-8 The low overall age and the paucity of elderly patients in these landmark trials limit the ability to derive information from them about long-term mortality outcomes in elderly patients. Most4,13-16 but not all17 sub-study analyses of elderly patients, enrolled in these landmark primary and secondary prevention trials and other large trials, have tended to show either no or a limited mortality benefit for ICD therapy. Smaller observational studies have also suggested the presence of a decreased mortality benefit for ICD therapy in elderly patients.18,19 Data derived from the large NCDR database identified age as a weak predictor of non-arrhythmic death among patients undergoing implantation of a defibrillator. Unfortunately these authors assessed only acute mortality rates observed during the implantation hospitalization.20 All of these manuscripts have been limited by the inclusion of select patient populations, retrospective study design, lack of long-term follow-up and a limited correlation of mortality outcomes with clinical data and ICD therapy outcomes. Prior publications failed to include 'a priori' study design plans to assess potential age-mortality associations and they were under-powered to clarify this issue. Given these limitations, it is not surprising that the issue of age as a factor to be considered when determining the appropriateness of an ICD implantation is not included in any of the published guidelines.21,22 Accordingly, additional prospective studies are needed to define more accurately patient populations, which are likely to derive the most benefit from this important therapy.
Several design characteristics augment the importance of the findings presented in this study. The Ontario ICD Database is an all inclusive registry (all Canadian implantation sites in Ontario are mandated to participate), which generates data from all ten adult implantation centers in that province. Thus the pre-selection biases, inherent in multicenter prospective trials and post-hoc retrospective analyses, are to some degree minimized in the analyzed patient data derived from this population-based cohort. Accordingly, the presented results may more accurately reflect a 'real world' scenario. Clinical information, follow-up processes and device based data were obtained, defined and analyzed by registry protocol. Existing national databases were utilized to clarify hospitalization information and cause of death. Based upon the broad-based patient population pool available for analysis and the longitudinal follow-up methodology employed, the presented mortality data is rigorous with a quality level that is consistent with data derived from a prospective, multicenter trial.
In this study, age was associated with a higher total mortality rate. However, the ability of the ICD to provide effective protection against life threatening ventricular arrhythmic events was independent of age. The findings suggest that the ICD can be expected to perform appropriately for its specified indication irrespective of age. The ability of the ICD to treat effectively potentially life-threatening ventricular arrhythmias independent of age, when combined with the higher cardiovascular and non-cardiovascular mortality rates observed among elderly patients, suggest that non-arrhythmic co-morbidities are important potential predictors of overall mortality. Accordingly, based upon the data presented in this study, when clinicians are formulating decisions about the risk-benefit ratio of defibrillator therapy in an elderly patient, they should not view age as an independent exclusion criterion but instead should consider it as one of many factors to be employed in the decision-making process.
In conclusion, this study provides important information in reference to the relationship between ICD efficacy and age-based mortality outcomes. The presented findings are sufficiently robust to assist clinicians and elderly patients when faced with these difficult clinical decisions. The findings also demonstrate the need for additional studies, which take into consideration competing mortality risk factors, to identify better risk stratification algorithms among patients being considered for ICD therapy. Since these studies are presently not available, clinicians should consider age and other competing mortality risk factors in the aggregate when formulating clinical recommendations for their patients.
- Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber D, Brown MW, Heo M. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996;335:1933-40.
- Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999;341:1882-90.
- Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML For The Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346: 877-83.
- Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH For The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-37.
- Goldenberg, I, Gillespie J, Moss AJ, Hall, WJ, Klein H, McNitt S, Brown MW, Cygankiewicz I, Zareba W. Long-term benefit of primary prevention with an implantable Cardioverter-defibrillator: an extended 8-year follow-up study of the Multicenter Automatic Defibrillator Implantation Trial II. Circulation 2010;122:1265-71.
- The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997;337:1576-83.
- Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, Mitchell LB, Green MS, Klein GJ, O'Brien B. Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation. 2000;101:1297-302.
- Kuck KH, Cappato R, Siebels J, Rüppel R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest : the Cardiac Arrest Study Hamburg (CASH). Circulation 2000;102:748-54.
- Yung D, Birnie D, Dorian P, Healey JS, Simpson CS, Crystal E, Krahn AD, Khaykin Y, Cameron D, Chen Z, Lee DS. Survival After Implantable Cardioverter-Defibrillator Implantation in the Elderly: Clinical Perspective. Circulation 2013;127:2383-2392.
- Goldenberg I, Vyas AK, Hall WJ, Moss AJ, Wang H, He H, Zareba W, McNitt S, Andrews ML; MADIT-II Investigators. Risk stratification for primary implantation of a cardioverter-defibrillator in patients with ischemic left ventricular dysfunction. J Am Coll Cardiol 2008; 51:288-96.
- Haines DE, Wang Y, Curtis J. Implantable cardioverter-defibrillator registry risk score models for acute procedural complications or death after implantable cardioverter-defibrillator implantation. Circulation 2011;123:2069-76.
- Reynolds MR, Cohen DJ, Kugelmass AD, Brown PP, Becker ER, Culler SD, Simon AW. The frequency and incremental cost of major complications among medicare beneficiaries receiving implantable cardioverter-defibrillators. J Am Coll Cardiol 2006;47:2493-7.
- Braunstein JB, Anderson GF, Gerstenblith G, Weller W, Niefeld M, Herbert R, Wu AW. Noncardiac Comorbidity Increases Preventable Hospitalizations and Mortality Among Medicare Beneficiaries with Chronic Heart Failure. J Am Coll Cardiol 2003;42:1226-33.
- Healey JS, Hallstrom AP, Kuck KH, Nair G, Schron EP, Roberts RS, Morillo CA, Connolly SJ. Role of the implantable defibrillator among elderly patients with a history of life-threatening ventricular arrhythmias. Eur Heart J 2007;28:1746–1749.
- Santangeli P, Di Biase L, Dello Russo A, Casella M, Bartoletti S, Santarelli P, Pelargonio G, Natale A. Meta-analysis: age and effectiveness of prophylactic implantable cardioverter-defibrillators. Ann Intern Med 2010;153:592–599.
- Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140–2150.
- Huang DT, Sesselberg HW, McNitt S, Noyes K, Andrews ML, Hall WJ, Dick A, Daubert JP, Zareba W, Moss AJ; MADIT-II Research Group. Improved survival associated with prophylactic implantable defibrillators in elderly patients with prior myocardial infarction and depressed ventricular function: a MADIT-II substudy. J Cardiovasc Electrophysiol 2007;18:833–838.
- Koplan BA, Epstein LM, Albert CM, Stevenson WG1: Survival in octogenarians receiving implantable defibrillators. Am Heart J 2006;152:714-9.
- Pellegrini CN, Lee K, Olgin JE, Turakhia MP, Tseng ZH, Lee R, Badhwar N, Lee B, Varosy PD. Impact of advanced age on survival in patients with implantable cardioverter defibrillators. Europace 2008;10:1296-301.
- Tsai V, Goldstein MK, Hsia HH, Wang Y, Curtis J, Heidenreich PA; National Cardiovascular Data Registry. Age differences in primary prevention implantable cardioverter-defibrillator use in U.S. individuals. J Am Geriatr Soc 2011;59:1589–1595.
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